title: Basic control of reperfusion effectively protects against reperfusion injury in a realistic rodent model of acute limb ischemia.
abstract: BACKGROUND
  Reperfusion injury is insufficiently addressed in current clinical management of acute limb ischemia. Controlled reperfusion carries an enormous clinical potential and was tested in a new reality-driven rodent model.
  
  
  RESULTS
  Acute hind-limb ischemia was induced in Wistar rats and maintained for 4 hours. Unlike previous tourniquets models, femoral vessels were surgically prepared to facilitate controlled reperfusion and to prevent venous stasis. Rats were randomized into an experimental group (n=7), in which limbs were selectively perfused with a cooled isotone heparin solution at a limited flow rate before blood flow was restored, and a conventional group (n=7; uncontrolled blood reperfusion). Rats were killed 4 hours after blood reperfusion. Nonischemic limbs served as controls. Ischemia/reperfusion injury was significant in both groups; total wet-to-dry ratio was 159+/-44% of normal (P=0.016), whereas muscle viability and contraction force were reduced to 65+/-13% (P=0.016) and 45+/-34% (P=0.045), respectively. Controlled reperfusion, however, attenuated reperfusion injury significantly. Tissue edema was less pronounced (132+/-16% versus 185+/-42%; P=0.011) and muscle viability (74+/-11% versus 57+/-9%; P=0.004) and contraction force (68+/-40% versus 26+/-7%; P=0.045) were better preserved than after uncontrolled reperfusion. Moreover, subsequent blood circulation as assessed by laser Doppler recovered completely after controlled reperfusion but stayed durably impaired after uncontrolled reperfusion (P=0.027).
  
  
  CONCLUSIONS
  Reperfusion injury was significantly alleviated by basic modifications of the initial reperfusion period in a new in vivo model of acute limb ischemia. With this model, systematic optimizations of according protocols may eventually translate into improved clinical management of acute limb ischemia.
authors.affiliation: Department of Cardiovascular Surgery, Inselspital, and University of Bern, Berne, Switzerland.
authors.forename: Florian
authors.initials: F
authors.lastname: Dick
authors.forename: Jianhui
authors.initials: J
authors.lastname: Li
authors.forename: Marie-Noëlle
authors.initials: MN
authors.lastname: Giraud
authors.forename: Christoph
authors.initials: C
authors.lastname: Kalka
authors.forename: Juerg
authors.initials: J
authors.lastname: Schmidli
authors.forename: Hendrik
authors.initials: H
authors.lastname: Tevaearai
mesh_terms: D000208:Acute Disease; D000818:Animals; D000925:Anticoagulants / Q000494:pharmacology; D004195:Disease Models, Animal; D004487:Edema / Q000188:drug therapy / Q000503:physiopathology / Q000517:prevention & control; D005260:Female; D005263:Femoral Artery / Q000000981:diagnostic imaging / Q000502:physiology / Q000601:surgery; D006493:Heparin / Q000494:pharmacology; D006614:Hindlimb / Q000098:blood supply*; D017078:Laser-Doppler Flowmetry; D008297:Male; D009119:Muscle Contraction; D016491:Peripheral Vascular Diseases / Q000188:drug therapy / Q000503:physiopathology / Q000517:prevention & control; D054070:Postthrombotic Syndrome / Q000188:drug therapy / Q000503:physiopathology / Q000517:prevention & control; D051381:Rats; D017208:Rats, Wistar; D012039:Regional Blood Flow; D015427:Reperfusion Injury / Q000188:drug therapy / Q000503:physiopathology* / Q000517:prevention & control*; D014111:Tourniquets; D014463:Ultrasonography
chemical_list: D000925:Anticoagulants; D006493:Heparin